ABSTRACT ? OVERALL The overall goal of the University of North Carolina at Chapel Hill (UNC) Core Center for Clinical Research (CCCR) is to enhance the design and conduct of clinical studies in Rheumatic and Musculoskeletal Diseases (RMDs) with a focus on osteoarthritis (OA), a particular strength of our research community. The pain and loss of function that results from arthritis, combined with its prevalence, make it a leading cause of disability. OA is the most common form of arthritis. Efforts are urgently needed to improve the management of people with OA, as well as the many other RMDs, to reduce pain, improve function and slow or stop disease progression. Like other chronic conditions, RMDs are not single diseases but rather heterogeneous conditions consisting of multiple phenotypes that differ in their underlying pathobiological mechanisms. If not taken into consideration, these phenotypic differences result in the testing of interventions designed to address specific mechanisms of action in the ?wrong? patients. Therefore, successful treatments for RMDs need to be targeted to, and tested in, specific subgroups or subtypes that share distinct underlying pathobiological, psychosocial and pain mechanisms consistent with the goal of precision medicine. Understanding and incorporating information about these phenotypes in clinical observational studies and trials will be crucial to move the field forward and is a major goal of our CCCR. Importantly, this pursuit will address the NIAMS long- range plan for clinical research which emphasizes that, ?clinical characterization of disease subtypes is critical to assessment of epidemiological data and efficient design of clinical trials in these disease areas.? The proposed UNC CCCR will build on our transformative Multidisciplinary Clinical Research Center (MCRC), Mitigating the Public Health Impact of OA. Although the CCCR will have a focus on OA, the analytical methods used for phenotyping and precision medicine will also be applied to other RMDs that are strengths within our research community including RA, lupus, and vasculitis. Our goal is to optimize the design, analysis and implementation of clinical studies and trials in OA and other RMDs to advance clinical care and public health efforts targeted toward individuals with these conditions through the following aims: 1) Administrative Core: Provide leadership, oversight, coordination, evaluation, and general administrative support for all CCCR activities; 2) Methodology Core: Provide a comprehensive and integrated set of RMD-focused services to optimize the quality, efficiency and innovation of the CCCR research community that includes local, national and international members; 3) Phenotyping and Precision Medicine Resource Core: Provide services that will add value to and optimize the design and implementation of clinical studies as well as develop innovative strategies to maximize the use and success of clinical phenotyping and precision medicine in RMDs, with a focus on OA.